BACKGROUND: Huntington's chorea, an hereditary movement disorder, is due to degeneration of neurons intrinsic to the striatum: the striata of affected patients exhibit marked decreases in the neurochemical markers for the cholinergic and GABAergic neurons whereas dopaminergic terminals are unaffected. PRELIMINARY OBSERVATIONS: Stereotaxic injection into rat striatum of 2.5 micrograms of kainate causes a degeneration of most neurons with cell bodies in the striatum. Ten days after treatment, there is a 70% decrement in the striatum of the neurochemical markers for cholinergic and GABAergic neurons, whereas the dopaminergic markers are not reduced. SPECIFIC AIMS: 1. The time course and specificity of the effects of kainate injected into rat striatum will be assessed by measuring several neurochemical markers for cholinergic, GABAergic and dopaminergic neurons. 2. The evidence that kainate acts by stimulating glutamate receptors will be assessed by determining the neurotoxic action of neuroexcitatory analogues of glutamate. 3. The metabolic consequences of kainate on striatal slices with respect to Na ion, H2O and ATP content will be determined to correlate neurotoxicity with its depolarizing action. 4. The morphologic consequences of kainate injection will be determined in Nissl-stained sections for neuronal cell bodies and by histofluorescent microscopy for dopaminergic terminals. 5. The effects of striatal injection of kainate on the nigro-striatal dopaminergic neurons will be examined with respect to changes in activity of tyrosine hydroxylase and turnover of dopamine. 6. The role of dopaminergic and cholinergic neurons in the rotatory behavior resulting from unilateral injection of kainate will be assessed by pharmacologic manipulations. SIGNIFICANCE: Striatal injection of kainate appears to be an animal model for Huntington's chorea on the basis of neurochemical, histologic and behavioral effects.